J Exp Clin Canc Res
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J Exp Clin Canc Res · Dec 2008
Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway.
The antiangiogenic agent cilengitide disrupts integrin binding to the extracellular matrix leading to apoptosis of activated endothelial cells. Integrins are also widely expressed in malignant glioma and integrin inhibitors may directly target tumor cells in this disease. Aim of the current study was to investigate effects of cilengitide on endothelial and glioma cells on molecular and cellular levels. ⋯ Cilengitide inhibits integrin-dependent signaling, causes disassembly of cytoskeleton, cellular detachment and induction of apoptosis in endothelial and glioma cells thereby explaining the profound activity of integrin inhibitors in gliomas. The combination of cilengitide with temozolomide exerted additive effects in glioma cells as observed clinically.